By: Michele Belizaire
Editor’s Note: In 2012, Colau et al published results of their efficacy study conducted in France to evaluate a non-hormonal therapy for menopausal hot flashes. [1] While on the FACTS fertility awareness online elective, Michele Belizaire summarized their study and its promising findings. To learn more about the management of peri-menopausal symptoms, you may sample our CME or register for Parts C, J or K of our online CME course. As a reminder, FACTS members receive a 20% discount on all CME course/conference registrations, so join FACTS today!
Introduction
The article by Colau et al [1] summarized below explains the challenge many women face with hot flashes in the peri- and post-menopausal period. The authors note up to 80% of women experience hot flashes, which can be socially embarrassing and diminish their quality of life. Although the hot flashes resolve in 50% of women, they persist in 30%. Hormone Replacement Therapy (HRT) has been the treatment of choice, as it relieves symptoms by 80-90%. However, studies have shown HRT increases the risk of breast cancer, and prescriptions for HRT decreased from 91 million in 2001 to 56.9 million in 2003.
“Up to 80% of women experience hot flashes, which can be socially embarrassing and diminish their quality of life.”
To find alternatives to HRT, various therapies have been used to treat symptoms, including SSRI’s, SNRI’s, antiepileptics, and “natural” medicines. BRN-01 (Actheane) is a homeopathic remedy used in France to treat menopausal hot flashes, and this study by Colau et al evaluated its efficacy.
Methodology
This was a 12-week double-blind, placebo-controlled study measuring the efficacy of BRN-01 versus placebo in post-menopausal women with hot flashes. Study participants were age 50 or older, had amenorrhea for at least 12 months, and had complained of at least five hot flashes in the 48 hours preceding the study. They were excluded if they:
(1) were currently using (or had used within 2 weeks before study enrollment) another treatment for hot flash symptoms,
(2) had a history of artificially-induced menopause, or
(3) were on medication to treat a different condition that could also decrease hot flash symptoms (e.g. clonidine for hypertension).
The treatment studied was BRN-01 (Actheane), a dilution of five homeopathic medications. The primary evaluation criterion was the effect of BRN-01 on hot flash score (HFS) vs. placebo effect. HFS was calculated by the product of the number of hot flashes per day and their intensity. The secondary criteria evaluated the difference between the beginning of the study and the 12th week of treatment. Criteria measured were difference in quality of life, severity of symptoms, effect on the patient’s professional and personal life, and adherence to the treatment protocol.
Results
The study took place between June 2010 and July 2011 with 50 patients in the BRN-01 group and 51 patients in the placebo group. At the start of the study, there was no average difference between the two groups regarding age, sociodemographic status, lifestyle habits, menopause onset, initial hot flash symptom onset, past treatment for symptoms, quality of life, or typical vasomotor symptoms.
When comparing results of the primary criterion, there was a significant difference in HFS after 12 weeks in the treatment group vs. the placebo group. The HFS in the BRN-01 group was 82.3 +/- 49.4 and in the placebo group it was 113.0 +/- 88.2 (p=0.0338).
When comparing results of the secondary evaluation criteria, a slightly greater improvement was seen in the treatment group vs. the placebo group, but this difference was not significant. For the difference in measurement of increased quality of life and reduction in intensity of symptoms, the p values were 0.2430 and 0.1774, respectively. The amount of reduction in strain on professional and personal life was not reported, but it was noted there was not a significant difference between the two groups for that parameter.
Adherence was lower in the placebo group compared to the treatment group, but this was not significantly different (p= 0.3773).
Discussion
This was the first study on the efficacy of BRN-01 on hot flash symptoms of menopause. The study showed a significant decrease in HFS using BRN-01, a homeopathic remedy, versus placebo. Although the decrease in HFS using BRN-01 is about ¾ of the decrease seen with HRT, it is comparable to the decrease seen with SSRI’s and noradrenaline.
“The study showed a significant decrease in hot flash score using BRN-01, a homeopathic remedy, versus placebo… (but it was) about ¾ of the decrease seen with hormone replacement therapy.”
This study is beneficial because it measured effectiveness of BRN-01 against no treatment and then analyzed its effectiveness compared to the standard treatment, providing a more thorough understanding of the options. Yet, the study design was limiting, given that all participants were from one European country (France). Different treatments can have different effects among individuals of various ethnic backgrounds; thus, future research could explore the efficacy of BRN-01 in women of other ethnicities. Prior studies analyzed the efficacy of other homeopathic medications on HFS using many of the same dilutions of substances used in BRN-01, but the countries of origin of the study participants were not identified in the article. This study is also somewhat dated.
In 2024, Pinkerton et al published research on elinzanetant, a selective neurokinin-1,3 receptor antagonist for the non-hormonal treatment of vasomotor symptoms (VMS) associated with menopause. Their research showed a significant improvement in baseline VMS compared to placebo. Additionally, this therapy achieved a clinically meaningful reduction in VMS according to FDA standards. [2] The study enrolled participants from various ethnic backgrounds and included women with artificially-induced menopause but it did not measure the efficacy of elinzanetant vs. HRT.
In 2021, Djapardy and Panay performed a review of research on several non-hormonal, non-pharmacologic treatments for VMS, including complementary medicine, isoflavones, red clover extract, CBT, and clinical hypnosis. The study showed varying degrees of efficacy with these treatment options, but none was as effective as HRT. [3]
“A review of research on several non-hormonal, non-pharmacologic treatments for vasomotor symptoms, including complementary medicine … showed varying degrees of efficacy with these treatment options, but none was as effective as HRT.”
This article highlights the fact that, relatively speaking, we are not far along in our study of natural ways to deal with peri-menopausal and menopausal symptoms in women. As of its publication, HRT was the only option shown to improve symptoms by at least 80%. Future studies should explore additional safe, effective alternatives for women with contraindications to HRT or who want a more “natural” approach.
References
[1] Colau, Jean-Claude et al. “Efficacy of a non-hormonal treatment, BRN-01, on menopausal hot flashes: a multicenter, randomized, double-blind, placebo-controlled trial.” Drugs in R&D 12,3 (2012): 107-19. doi:10.2165/11640240-000000000-00000
[2] Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. 2024;332(16):1343–1354. doi:10.1001/jama.2024.14618
[3] Veronica Djapardy, Nicholas Panay. Alternative and non-hormonal treatments to symptoms of menopause: Best Practice & Research Clinical Obstetrics & Gynecology, 2022;81 (45-60): 1521-6934. org/10.1016/j.bpobgyn.2021.09.012
ABOUT THE AUTHOR
Michele Belizaire
Michele Belizaire is a fourth-year medical student at Philadelphia College of Osteopathic Medicine-Georgia in Suwanee, GA. She completed her undergraduate education at Florida State University in Tallahassee, FL. She plans to pursue residency in family medicine and is enthusiastic about offering her future patients a full scope of care and education so they understand their options. She enrolled in the FACTS elective to gain a better understanding of natural family planning methods and ways to share them with patients to fulfill this goal.
